1. Academic Validation
  2. Photoactive Parietin-loaded nanocarriers as an efficient therapeutic platform against triple-negative breast cancer

Photoactive Parietin-loaded nanocarriers as an efficient therapeutic platform against triple-negative breast cancer

  • Int J Pharm. 2023 Jul 8;123217. doi: 10.1016/j.ijpharm.2023.123217.
Abdallah M Ayoub 1 Muhammed S Atya 2 Ahmed M Abdelsalam 3 Jan Schulze 2 Muhammad U Amin 2 Konrad Engelhardt 2 Matthias Wojcik 2 Damiano Librizzi 4 Behrooz H Yousefi 4 Usman Nasrullah 5 Josef Pfeilschifter 5 Udo Bakowsky 6 Eduard Preis 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
  • 2 Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany.
  • 3 Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
  • 4 Center for Tumor Biology and Immunology (ZTI), Core Facility Molecular Imaging, Department of Nuclear Medicine, University of Marburg, Germany.
  • 5 Institute of General Pharmacology and Toxicology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • 6 Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany. Electronic address: ubakowsky@aol.com.
  • 7 Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany. Electronic address: eduard.preis@pharmazie.uni-marburg.de.
Abstract

The application of photodynamic therapy has become more and more important in combating Cancer. However, the high lipophilic nature of most photosensitizers limits their parenteral administration and leads to aggregation in the biological environment. To resolve this problem and deliver a photoactive form, the natural photosensitizer parietin (PTN) was encapsulated in poly(lactic-co-glycolic acid) nanoparticles (PTN NPs) by emulsification diffusion method. PTN NPs displayed a size of 193.70 nm and 157.31 nm, characterized by dynamic LIGHT scattering and atomic force microscopy, respectively. As the photoactivity of parietin is essential for therapy, the quantum yield of PTN NPs and the in vitro release were assessed. The antiproliferative activity, the intracellular generation of Reactive Oxygen Species, mitochondrial potential depolarization, and lysosomal membrane permeabilization were evaluated in triple-negative breast Cancer cells (MDA-MB-231 cells). At the same time, confocal laser scanning microscopy (CLSM) and flow cytometry were used to investigate the cellular uptake profile. In addition, the chorioallantoic membrane (CAM) was employed to evaluate the antiangiogenic effect microscopically. The spherical monomodal PTN NPs show a quantum yield of 0.4. The biological assessment on MDA-MB-231 cells revealed that free PTN and PTN NPs inhibited cell proliferation with IC50 of 0.95 µM and 1.9 µM at 6 J/cm2, respectively, and this can be attributed to the intracellular uptake profile as proved by flow cytometry. Eventually, the CAM study illustrated that PTN NPs could reduce the number of angiogenic blood vessels and disrupt the vitality of xenografted tumors. In conclusion, PTN NPs are a promising Anticancer strategy in vitro and might be a tool for fighting Cancer in vivo.

Keywords

CAM model; MDA-MB-231; PLGA nanoparticles; Photodynamic therapy; antiangiogenesis; physcion; reactive oxygen species.

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